Heritability of Apnea of Prematurity: A Retrospective Twin Study

BACKGROUND: Apnea of prematurity (AOP) is a disturbance in respiratory rhythm defined by idiopathic pauses in breathing that reduce blood oxygen levels and/or heart rate. It is a major clinical problem among preterm infants. OBJECTIVES: The primary goal of this study was to estimate the genetic susceptibility to AOP in a cohort of preterm twins. A secondary aim was to identify risk factors associated with AOP in this cohort. METHODS: A single-center, retrospective study (2000-2008) was performed by using data from 317 premature twin pairs (<36 weeks' gestational age). Heritability estimates were determined by comparing intrapair AOP concordance between 56 monozygotic and 161 dizygotic twin pairs by using structural equation modeling. Risk factors of AOP among a cohort of 543 premature twins were assessed by using mixed-effects logistic regression. RESULTS: The heritability of AOP was 87% (95% confidence interval [CI]: 0.64-0.97) among same-gender twins. A gender-dependent model revealed that genetic factors accounted for 99% of the variance in male twins (95% CI: 0.89-1.00) and 78% of the variance in female twins (95% CI: 0.49-0.94). Significant risk factors for AOP were low gestational age (P < .001), cesarean delivery (P = .017), and conception through assisted reproductive technologies (P = .008). CONCLUSIONS: These findings suggest that AOP has an important genetic basis underlying this developmental-related disorder of respiratory control. Future genomic studies may provide information on pathophysiological mechanisms that underlie AOP. Pediatrics 2010;126:e779-e787